Off-label prescribing; should it be one of our New Year’s resolutions? #PoliticalSpeak #MSBlog #OffLabel
“On reflection one of the most important issues we have tried to address on this blog in 2015 is access to effective DMTs for people with MS (pwMS) who live in resource-poor settings. My personal experiences of what it is like to be a pwMS living in a resource-poor country remains the primary motivator for this policy initiative. Barts-MS plans to take this policy forward in 2016 with the help of several new partners.”
“A part of the solution we have been promoting the use of off-label, cheaper, alternative DMTs to treat MS. The following is our Barts-MS essential off-label DMT list (click on each drug for more information):
*on the 19th WHO Model List of Essential Medicines (April 2015)
We think there is enough direct, or indirect, efficacy and safety data to support the use of these drugs as DMTs in MS.”
“Interestingly, we have a lot of resistance to this policy from multiple sources; internally from within our University (Policy Unit), Pharma, colleagues (from both resource rich and poor countries), and even several of the MS Charities. Our policy unit feels that there is far too much inappropriate off-label prescribing in the world and that we should really stick to the policy of only prescribing on-label. Pharma as it challenges their business model. Colleagues in resource-rich countries feel the medicolegal risks of prescribing off-label are too high and can’t be justified. Clinicians in resource-poor settings don’t like double-standards; why should they apply lower standards to treating pwMS in their countries? Surely, pwMS in resource-poor countries should have access to the same DMTs with appropriate risk:benefit assessments to those living in richer countries? The MS Charities favour lobbying Pharma to make available licensed DMTs at a cheaper price to pwMS in resource poor countries. The latter solution exists in many other disease areas; why not in MS? I suspect there is still a perception that MS is a ‘rich-country’ disease and is too rare in developing countries to warrant a sponsored drug-access scheme. Herein lies the problem. MS is not only a rich-country disease, we are seeing increasing incidence rates across the developing world. We mustn’t forget pwMS who live in these countries, they need our help. If we want to reduce the burden of MS across the world we need workable policies so that MSers living in resource-poor countries get access to the same health care and treatments as MSers living in the developed world.”
“Interestingly, we have a lot of resistance to this policy from multiple sources; internally from within our University (Policy Unit), Pharma, colleagues (from both resource rich and poor countries), and even several of the MS Charities. Our policy unit feels that there is far too much inappropriate off-label prescribing in the world and that we should really stick to the policy of only prescribing on-label. Pharma as it challenges their business model. Colleagues in resource-rich countries feel the medicolegal risks of prescribing off-label are too high and can’t be justified. Clinicians in resource-poor settings don’t like double-standards; why should they apply lower standards to treating pwMS in their countries? Surely, pwMS in resource-poor countries should have access to the same DMTs with appropriate risk:benefit assessments to those living in richer countries? The MS Charities favour lobbying Pharma to make available licensed DMTs at a cheaper price to pwMS in resource poor countries. The latter solution exists in many other disease areas; why not in MS? I suspect there is still a perception that MS is a ‘rich-country’ disease and is too rare in developing countries to warrant a sponsored drug-access scheme. Herein lies the problem. MS is not only a rich-country disease, we are seeing increasing incidence rates across the developing world. We mustn’t forget pwMS who live in these countries, they need our help. If we want to reduce the burden of MS across the world we need workable policies so that MSers living in resource-poor countries get access to the same health care and treatments as MSers living in the developed world.”
“The New Year will therefore see us launch a new initiative to focus on MS issues that are unique and pertinent to the pwMS living in developing countries and/or in resource poor settings; the latter includes refugees, illegal immigrant populations and possibly the medically uninsured living in developed countries. If you are a healthcare professional (HCP) looking after pwMS in these environments and want to help and be part of this initiative please do not hesitate to contact us. As will all policy initiatives the more people who get involved the better. We need volunteers!”
“We still have an open survey running to see how much support we have for the off-label prescribing component of our policy. When I last checked the results over 80% of you were supportive of our efforts. Do you still feel this way?”
“Let’s make 2016 the year of hope and effective treatment options for all people living with MS. Happy New Year!”
“We still have an open survey running to see how much support we have for the off-label prescribing component of our policy. When I last checked the results over 80% of you were supportive of our efforts. Do you still feel this way?”
“Let’s make 2016 the year of hope and effective treatment options for all people living with MS. Happy New Year!”
CoI: multiple
Prof G do you think cladribine has the edge over the other drugs on your off label list? Shouldn't you be simplifying things and recommending fewer drugs? This is the principle of the WHO essential drug list.
No ProfG and yet: This is a matter of ongoing discussions within BartsMS. I agree it made sense to focus, say on the top 3, but we really don't know which drugs are available at an affordable price in each country.
Re: "WHO essential drug list."Very important point; I have just checked the WHO 2015 Essential Drug list and of our list only methotrexate, azathioprine, cyclophosphamide, rituximab and fludarabine (tablets) are on the list. Interestingly, cladribine, mitoxantrone and leflunomide are not on the list; arguably the 3 drugs with the most phase 3 data to support their use in MS. Therefore, if we wanted to make the case for using off-label drugs in resource-poor settings based on the WHO Essential Drug list then we would have to focus on the 5 drugs on the list. As DrK has said this will be up for discussion. http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf
Re: "..do you think cladribine has the edge over the other drugs on your off label list?"No not necessarily, it all depends on whether or not the PwMS and their HCP decides on an induction vs. maintenance-escalation strategy. Similarly, availability and price may vary depending on what country is involved. I think having options will be helpful; not all PwMS will want an induction therapy hence drugs such as azathioprine, methotrexate and leflunomide may be more appealing. Another issue is opportunistic infections; for example TB which in 2015 topped the list of infectious killers globally. Using induction agents in healthcare environments with a high-rate of endemic TB would be risky. I suspect the neurologists working in these settings may opt for safer less risky off-label DMTs. Finally, the availability of cheap anti-CD20 (rituximab) monoclonal biosimilars may be the game-changer. The benefit:risk of anti-CD20 therapies looks extremely good, with a low opportunistic infection risk when used as a monotherapy. I was very happy for MSers to see that rituximab has made it onto the WHO Essential drug list.
Finally, I have now put them in alphabetical order and highlighted which ones are on the WHO Essential Medicines list to make the point that at present we are not favouring any one treatment strategy (induction vs. maintenance-escalation) or any specific off-label drug.
We should remember the WHO's Essential Medicines list does not even include the diagnosis of Multiple Sclerosis among the diseases covered. Given its relatively focussed license for hairy cell leukemia it is therefore not surprising that Cladribine is not among the listed drugs though outperfoming all bar Rituximab by a mile or more when efficacy, safety and convenience are considered.A first step must therefore be to get MS on the WHO map in terms of essential medicines. As far as I'm aware this has been undertaken only in conjunction with Azathioprine (http://www.who.int/selection_medicines/committees/expert/20/applications/Azathioprine.pdf). We've reported about the evidence in favour of Aza a number of times (http://multiple-sclerosis-research.blogspot.com/2014/11/cheap-as-chips-azathioprine-is-better.html).
This refugee crisis in Europe will be interesting to see materialise in 20 years or so as those of central Asian ancestry settle in cold north European locations and potentially endure the consequences of it.Caucasian Europeans are decreasing and ethnic groups are growing. Their bodies are not designed for life here, not from an evolutionary stand point, however. This is a health ticking time bomb, perhaps.
Nothing like a warm sweater and abit of vitamin D supplementation. I do not think Caucasian Europeans are decreasing they are not moving anywhere.
So have all my West Indian friends been a health ticking time bomb?
They're not breeding, MouseDoc. Germany's population crisis is proof positive of this.
I fully support this initiative, since even let it clear here on the Blog. The biggest problem is awareness among neurologists that …